INS and Nephropathy: Our results are also indicative of an association between doxepin-aggravated hyperglycemia—also related to decreased phospho-Akt and GLUT4 expression in insulin signaling—and impairment in glucose tolerance, a decrease in IS, and an increase in IR; thus, decreases in renal antioxidant enzyme levels and increases in renal ROS levels may have exacerbated nephropathy.